Genetic engineering scopolamine

Some Hyoscyamus and Duboisia root cultures accumulate scopolamine as a major product (Robins and Walton, 1993). In contrast, only traces of scopolamine were found in D. stramonium roots. This implies that the expression of hyoscyamine 6 3-hydroxyIase (H6H) that forms the 6,7-epoxide is variable and, hence, this enz)mie has also been targeted for genetic engineering. 

Nevertheless, genetic engineering of a key enzyme in a chosen pathway does not always result in the enhancement of the end product thus, overexpression of pmt gene carried out in A. belladonna resulted in a 5-fold increased in pmt transcript level but an unchanged tropane alkaloid profile (hyoscyamine and scopolamine), as well as the tropane alkaloids biosynthetic precursors tropine, pseudotropine and tropinone which were not affected [134-135], Similarly, the overexpression of tobacco pmt gene in Dubosia hybrid hairy root cultures produced amounts of tropane alkaloid similar to control roots [131, 136]. All these results seem to indicate the presence of different points of control in the tropane alkaloid metabolic pathway. 

It has been demonstrated that H6H catalyses the formation of scopolamine from hyoscyamine. Besides, the encoding h6h gene has been identified and sequenced. Thus, the genetic engineering of this metabolic step offers great interest for scopolamine enhancement in... 

Scopolamine is a more costly derivative of atropine it has an epoxide function (6). Therefore, many studies concern the bioconversion of atropine (/-hyoscyamine) to scopolamine. The isolation of the enzymes involved and the subsequent cloning of the genes open new avenues for the production of scopolamine, either by genetic engineering of plants or by introducing the gene(s) responsible into microorganisms which could then effectively perform the desired bioconversion. 

Jouhikainen, K, Lindgren, L., Jokelainen, T., Hiltunen, R., Teeri, T. H., and Oksman-Caldentey, K. M. (1999) Enhancement of scopolamine production in Hyoscyamus muticus L. hairy root cultures by genetic engineering. Planta 208, 545-551. 

Jouhikainen K et al (1999) Enhancement of scopolamine production in Hyoscyamus muticus L. hairy root cultures by genetic engineering. Planta 208 545-551... 

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